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1、萬方數(shù)據(jù)英文摘要EffectofmTORsignalingpathwayonischemia—reperfusioninjuryinratsColledgeofPharmaceuticalScience,ZhejiangUniversityPharmacyCandidateforMasterSupervisorAbstractHuadanZhangProf.LinghuiZengobjective:CerebralischemiaiSaseriousdiseasewhichlcadstoextensivecerebraldamageandseriousneurologic
2、aldeficits.Tillnow,tissueplasminogenactivator(tPA)remainstheonlyapproveddrugproventOimproveclinicaloutcomew翊、ischemicstroke.However.theuseoftPAiSlimitedbecauseofanincreasedriskofhemorrhagefewhourspost—stroke.Therefore,itisurgentforinvestigatingnewtherapeuticstrategiesforisehemicstroke。Mam
3、maliantargetofraparnycin(roTOR)isacriticalregulatorofcellgrowthandmetabolismthatisimplicatedinmanydiseases.Rapamycin,aninhibitorofmTOl乙wasdiscoveredtoantagonizetheanti—apoptoticsignalsandstimulateautophagytomaintainnormalcellmetabolism.Ithasalsodemonstratedeffectsinbehavioralandlearningin
4、theanimalmodeloftraumaticbraininjury.However,theeffectandmechanismofmTOR—mediatedprotectioninischemicstrokeisunclear.Inthepresentstudy,weexploredwhetherthemTORsignalingpathwayisinvolvedinischemia-reperfusioninjuryinSDrats.Methods:wecarriedoutmiddlecerebralarteryocclusion(MCAO)withsutureme
5、thodinSDratstomimictheprocessofhumancerebralischemia.neneurologicalcriterionofratsatdifferenttimepointsafterMCAOmodelingWasmonitored.ThechangesofthemTORsignalingpathwayindifferenttimepointandbrainareaweredetectedusingWesternBlotafterMCAOmodeling.TTCstainingwasusedtoanalyzetheinfarctsizebe
6、foreandaftermodeling.FJBstainingWascarriedouttomeasureapoptoticcells.CD68fluorescentstainingWasusedtomeasurethenumberofmicroglialcell.Results:mTORpathwaywasactivatedTV萬方數(shù)據(jù)浙江大學(xué)碩士學(xué)位論文英文摘要60minutesafterMCAOintheischemicpenumbra.Aswesetischemictimefor1handobservedmTORpathwayatdifferentinterva
7、lsofreperfusion,wefoundthatactivationofmTORpathwaykeptathigherlevelfrom6hhoursafterperfusion.Long-termmonitoringafterischemiashowedthatmTORsignalingpathwaystillkeptathighlevelfrom2weeks.Pre·administrationandpost—administrationofrapamycinsignificantlyimprovedneurolog